OF HIS TREATMENT FOR RELAPSED MULTIPLE MYELOMA. Understanding the steps on your treatment journey

Transcription

1 EMMETT TAKES CHARGE OF HIS TREATMENT FOR RELAPSED MULTIPLE MYELOMA Understanding the steps on your treatment journey APPROVED USE KYPROLIS (carfilzomib) is a prescription medication used to treat patients with relapsed or refractory multiple myeloma who have received one to three previous treatments for multiple myeloma. KYPROLIS is approved for use in combination with dexamethasone or with lenalidomide plus dexamethasone, which are other medicines used to treat multiple myeloma. Heart problems: KYPROLIS can cause heart problems or worsen pre-existing heart conditions. Death due to cardiac arrest has occurred within one day of KYPROLIS administration. Before starting KYPROLIS, you should have a full medical work-up (including blood pressure and fluid management). You should be closely monitored during treatment. Please see additional Important Safety Information on page 17.

2 Meet Emmett. Like you, he has important decisions to make. Emmett was diagnosed with multiple myeloma a few years ago, and has already received treatment. Today, Emmett learned his multiple myeloma has returned or relapsed. As a result, he has some important choices to make with his doctor. He wants to think about what s most important to him because he knows what he decides will have an impact on the journey ahead. For example: Is his primary goal to treat his relapsed multiple myeloma to help delay it from getting worse? Is he concerned about how often his appointments will be? Are both of these considerations equally important? COMMUNICATE WHAT S IMPORTANT. Make sure you tell your doctor what s most important to you. As you review treatment options with your doctor, be honest about what you want. Kidney problems: There have been reports of sudden kidney failure in patients receiving KYPROLIS. Your kidney function should be closely monitored during treatment. Tumor lysis syndrome (TLS): Cases of TLS have been reported in patients receiving KYPROLIS, including fatalities. You should be closely monitored during treatment for any signs of TLS. Please see additional Important Safety Information on page 17. 2

3 STEP 1: SET YOUR GOALS Time to take charge. Decide on goals that work for you. Emmett talked over treatment options with his family and doctor. He decided his primary goal is to treat his relapsed multiple myeloma to help delay it from getting worse. After discussing Emmett s goals, his doctor recommended a KYPROLIS (carfilzomib) based combination. KYPROLIS based combinations are KYPROLIS +dexamethasone (called K+d) or KYPROLIS +Revlimid (lenalidomide)+dexamethasone (called K+Rd). WHAT ARE YOUR RELAPSE TREATMENT GOALS? Ask your doctor if a KYPROLIS based combination (K+d or K+Rd) could help you. Continue for your multiple myeloma glossary. Lung damage: Cases of lung damage have been reported in patients receiving KYPROLIS, including fatal cases. Pulmonary hypertension (high blood pressure in the lungs): There have been reports of pulmonary hypertension in patients receiving KYPROLIS. Please see additional Important Safety Information on page 17. 3

4 Your multiple myeloma glossary. Your doctor may use new words and terms when discussing your multiple myeloma. ASK HIM OR HER TO EXPLAIN ANYTHING THAT ISN T CLEAR. Monoclonal protein (M protein) 1 This is an abnormal protein produced by myeloma cells. The amount of M protein in the blood is used to assess the severity of the disease and your response to treatment. Overall Survival (OS) 1 OS is a measure used in clinical studies to gauge how long people live after being diagnosed or starting treatment. OS helps doctors understand how well a treatment works. Plasma Cells 2 Plasma cells are a type of white blood cell that is made in the bone marrow. These cells make antibodies to help the body fight off infection and disease. In multiple myeloma, plasma cells become abnormal. These cancerous plasma cells build up in the bone marrow, crowding out healthy cells. The cancerous cells may also cause tumors which can damage and weaken bones. These cancerous plasma cells can also leave the bone marrow and form tumors in soft tissues, causing pain and other problems. In addition, cancerous plasma cells make M proteins, which cannot help fight infections. M proteins are not needed by the body, and cause the blood to thicken. This blood thickening can damage the kidneys. Progression-free Survival (PFS) 1 PFS is a measure in a clinical study that gauges how long treatment keeps your myeloma at bay. It measures how long patients are alive without the disease getting worse after being diagnosed or starting treatment. Like OS, PFS helps doctors assess whether a treatment is working. A longer PFS is better than a shorter one. Response Rate 1,3 Your response rate refers to how well you are responding to treatment. Response includes measurements of M protein in the blood or urine. Possible response rates include: PR VGPR CR SCR Partial Response For more information on response rates, go to page 11. Very Good Partial Response Complete Response Stringent Complete Response 4

5 STEP 2: COMMIT TO THE DOSING REGIMEN KYPROLIS (carfilzomib) has several dosing options. 4 Emmett s doctor explained it is important to follow the recommended dosing schedule. Emmett also learned that KYPROLIS is given as an infusion in a doctor s office, a clinic, or hospital. 4 This means that you ll receive the medicine by intravenous (IV) infusion. An infusion is a way to put fluids, including medicine, into the bloodstream through a vein. 5 FOLLOW THE DOSING SCHEDULE RECOMMENDED BY YOUR DOCTOR. If you have any questions, be sure to ask your doctor. Continue for dosing schedule. Lung complications: Shortness of breath was reported in patients receiving KYPROLIS. Your lung function should be closely monitored during treatment. High blood pressure: Cases of high blood pressure, including fatal cases, have been reported in patients receiving KYPROLIS. Your blood pressure should be closely monitored during treatment. Please see additional Important Safety Information on page 17. 5

6 How is KYPROLIS (carfilzomib) given? 4 KYPROLIS is an infusion given in a doctor s office, clinic, or hospital. Revlimid (lenalidomide) is taken as a pill and dexamethasone can be infused or taken as a pill. These treatments are given in cycles. The length of each treatment cycle is 28 days. See the calendars below for the correct treatment days. The calendars also show you what your treatment schedule might be. Your doctor will give you a lower dose for the first week of your first treatment cycle: Days 1 and 2 for twice weekly dosing Day 1 for once weekly dosing If you tolerate the dose, your doctor may increase the dose of your other infusions of KYPROLIS. KYPROLIS +Rd (K+Rd) (KYPROLIS +lenalidomide +dexamethasone) WEEK 1 WEEK 2 WEEK 3 CYCLES 1-12: Example WEEKS 1-3 Dexamethasone on the first day KYPROLIS for 2 days in a row Lenalidomide once daily on Days 1-21 In Cycles 13-18, KYPROLIS infusion only during Weeks 1 and 3 Treatment Schedule THIS REGIMEN IS CALLED A TRIPLET BECAUSE 3 DRUGS ARE GIVEN WEEK 4 WEEK 1 WEEK 2 WEEK 3 WEEK CYCLES 13-18: Example WEEK 4 No infusion of KYPROLIS Dexamethasone on Day 22 Your doctor should stop your treatment with KYPROLIS after Cycle 18, or it may be stopped earlier if you experience side effects that cannot be managed or tolerated. KYPROLIS 10-minute IV infusion KYPROLIS rest days KYPROLIS +d (K+d) (KYPROLIS +dexamethasone) Treatment Schedule THIS REGIMEN IS CALLED A DOUBLET BECAUSE 2 DRUGS ARE GIVEN IV = intravenous. WEEK 1 WEEK 2 WEEK 3 WEEK 4 WEEK 1 WEEK 2 WEEK 3 WEEK 4 TWICE WEEKLY TREATMENT CYCLE: Example ONCE WEEKLY TREATMENT CYCLE: Example WEEKS 1-3 KYPROLIS and dexamethasone for 2 days in a row WEEK 4 No infusion of KYPROLIS You should receive dexamethasone 2 days in a row, on the same days of the week as your infusion schedule KYPROLIS 30-minute IV infusion at a lower dose KYPROLIS rest days WEEKS 1-3 KYPROLIS and dexamethasone 1 day each week WEEK 4 No infusion of KYPROLIS For Cycles 1-9, you should still receive dexamethasone 1 day, on the same day of the week as your infusion schedule For Cycles 10 and later, you will not receive dexamethasone KYPROLIS 30-minute IV infusion at a higher dose KYPROLIS rest days Infusion reactions: Symptoms of infusion reactions included fever, chills, joint pain, muscle pain, facial flushing and/ or swelling, vomiting, weakness, shortness of breath, low blood pressure, fainting, chest tightness, and chest pain. These symptoms can occur immediately following infusion or up to 24 hours after administration of KYPROLIS. If you experience any of these symptoms, contact your doctor immediately. Please see additional Important Safety Information on page 17. 6

7 STEP 3: PREPARE FOR CHALLENGES Know what to expect. Be prepared for ups and downs along the way. Emmett has learned that living with multiple myeloma means having good days and some not-so-good days. But he s also learned to prepare for the challenges and ask for help when he needs it. Emmett s daughter has been his care partner and helps take him to appointments. Is there someone who could be your care partner? Emmett also knows he should prepare for possible side effects from treatment. When he knows what to expect, Emmett can talk to his doctor about how he can be proactive. Tell your doctor about any side effects you are experiencing. Also, be sure to ask questions you have about your multiple myeloma and the treatments that are available. Writing your questions down before your appointment may help you remember what to ask. Continue to learn how can help you find resources. What are the possible side effects of KYPROLIS (carfilzomib)? The most common side effects occurring in at least 20% of patients receiving KYPROLIS in the combination therapy trials are: low red blood cell count, low white blood cell count, diarrhea, difficulty breathing, tiredness (fatigue), low platelets, fever, sleeplessness (insomnia), muscle spasm, cough, upper airway (respiratory tract) infection, and decreased potassium levels. Please see additional Important Safety Information on page 17. 7

8 We re here for you. Discover how Amgen Assist 360 TM can help refer you to resources most important to you. Amgen Assist 360 Nurse Ambassadors Amgen Nurse Ambassadors are a single point of contact who takes the time to help you and your caregiver identify which types of assistance are most important to you. They will assist you in finding resources, so that you and your caregiver can focus on your treatment. They do not, however, provide medical advice or case management services.* CO-PAY AND REIMBURSEMENT RESOURCES Whatever insurance you have even if you have none the Nurse Ambassador can help you understand how your Amgen medicine may be covered and refer you to programs that may be able to help you afford it, such as Amgen FIRST STEP or other independent nonprofit organizations. REFERRALS TO RESOURCES FOR DAY-TO-DAY LIVING* Sometimes you need someone who knows what you re going through. The Nurse Ambassador can refer you to independent nonprofit organizations that may provide you with community resources, one-on-one counseling services, and local support groups. HELP FINDING TRANSPORTATION AND LODGING ASSISTANCE If you need assistance with travel that s connected to your therapy, the Nurse Ambassador can put you in touch with independent nonprofit organizations that may provide you help with gas, tolls, parking, airfare, and lodging. MEDICATION ANSWERS If you have any questions about your Amgen medicine, the Nurse Ambassador may help you find the answers. *Patients should always talk to their healthcare provider about any medical decisions or concerns they may have. Resources include referrals to independent nonprofit patient assistance programs. Eligibility for resources provided by independent nonprofit patient assistance programs is based on the nonprofits criteria. Amgen has no control over these programs and provides referrals as a courtesy only. Support, Simplified. CALL 888-4ASSIST ( ) Monday to Friday 9 am to 8 pm EST VISIT AMGENASSIST360.COM/ENROLL Please see Important Safety Information on page 17. 8

9 STEP 4: REACH & MANAGE YOUR BEST RESPONSE Get the best possible response for you. Ask your doctor how long you should stay on therapy. Today, Emmett found out he reached an important step: Complete Response (CR) with a KYPROLIS (carfilzomib) based combination (K+Rd or K+d). Congrats! Emmett s doctor recommended that he stay on therapy after he reached his best response Complete Response. Ask your doctor what s right for you. MULTIPLE MYELOMA DOESN T TAKE A BREAK. NEITHER SHOULD YOU. Talk to your doctor about how long you should stay on therapy. Keep checking your response over time. When you see your doctor, ask how you are responding to treatment. Your goal should be the best response possible for you. Response is one measure of how well your treatment is working. To measure your response to treatment, your blood and/or urine may be tested for M proteins an abnormal protein made by myeloma cells. High M protein levels are 1 possible sign of active multiple myeloma. Ask your doctor what your M protein levels are. 1 Another way to determine a response to treatment is to test the bone marrow for the presence of abnormal plasma cells. High levels of abnormal plasma cells in the bone marrow may be another indicator of active multiple myeloma. 6 Here are 4 possible responses to treatment, from less favorable to more favorable 3 : PR VGPR Partial Response - 50% or greater decrease in M proteins in the blood - 90% or greater decrease in M proteins in the urine - 50% or greater decrease in size of soft tissue tumor (if applicable) CR Very Good Partial Response - 90% or greater decrease in M proteins in the blood - Decrease in M proteins in urine SCR Complete Response These definitions have been simplified. - No detectable M proteins in the blood and urine - Fewer than 5% abnormal plasma cells in bone marrow - No detectable soft tissue tumors Stringent Complete Response - No detectable M proteins in the blood and urine - No detectable abnormal plasma cells in bone marrow - No detectable soft tissue tumors Blood clots: There have been reports of blood clots in patients receiving KYPROLIS. If you are at high risk for blood clots, your doctor can recommend ways to lower the risk. If you are using KYPROLIS in combination with dexamethasone or with lenalidomide plus dexamethasone, your doctor should assess and may prescribe another medicine to help lower your risk for blood clots. If you are using birth control pills or other medical forms of birth control associated with a risk of blood clots, talk to your doctor and consider a different method of birth control during treatment with KYPROLIS in combination with dexamethasone or with lenalidomide plus dexamethasone. Please see additional Important Safety Information on page 17. 9

10 K+Rd: Consider the proven results of KYPROLIS (carfilzomib) when added to Revlimid (lenalidomide) and dexamethasone. * K+Rd delayed multiple myeloma from getting worse by almost 9 months longer than R+d months (median ) 17.6 months (median VS ) KYPROLIS +Revlimid +dexamethasone (K+Rd) results (396 patients) Revlimid +dexamethasone (R+d) results (396 patients) Emmett s doctor explained that in the clinical study almost 9 10 OUT OF patients responded to treatment with K+Rd. 4 * In a clinical study of 792 patients with relapsed or refractory multiple myeloma who had received 1-3 prior therapies, 396 patients received KYPROLIS in combination with Revlimid and dexamethasone, and 396 received Revlimid in combination with dexamethasone. The study compared how long patients lived without their disease getting worse and how patients responded to treatment. 4 The median is the middle number in a group of numbers arranged from lowest to highest. Continue to see how many patients with relapsed multiple myeloma achieved complete response or better in clinical studies. Severe bleeding problems: Fatal or serious cases of bleeding problems have been reported in patients receiving KYPROLIS. Your doctor should monitor your signs and symptoms of blood loss. Very low platelet count: Low platelet levels can cause unusual bruising and bleeding. You should have regular blood tests to check your platelet count during treatment. Please see additional Important Safety Information on page

11 PATIENTS (%) CUMULATIVE PERCENTAGE OF PATIENTS REACHING CR OR BETTER (%) More patients on the K+Rd regimen had a response to treatment. 4 CLINICAL STUDY RESULTS: PATIENTS ON K+Rd vs R+d 87% 67% OVERALL RESPONSE RATE (Partial Response or better) 70% 40% VERY GOOD PARTIAL RESPONSE or better Key: 32% 9% COMPLETE RESPONSE or better K+Rd 396 patients R+d 396 patients 3xAS MANY PATIENTS achieved a complete response or better with K+Rd vs R+d 4 MORE PATIENTS ON K+Rd vs R+d REACHED CR OR BETTER AT EVERY TIME POINT MEASURED* WHAT DO THE RESPONSE RATES MEAN? 1,3 Overall Response Rate = The percentage of patients in the clinical study with at least a partial response to treatment Very Good Partial Response or better = The percentage of patients in the clinical study with at least a very good partial response Complete Response or better = The percentage of patients in the clinical study with at least a complete response The longer patients stayed on treatment, the better their chances of reaching Complete Response (CR) or better Emmett understands that staying on treatment as long as possible can help him achieve a better response TIME FROM START OF TREATMENT KYPROLIS was discontinued after Cycle 18 PATIENTS ON K+Rd PATIENTS ON R+d Your doctor should stop your treatment with KYPROLIS after Cycle 18, or it may be stopped earlier if you experience side effects that cannot be managed 15 * After the initial results of the clinical study were reported, the investigators decided to look at the cumulative number of patients who reached a complete response or better over time. This was not an objective of the clinical study. Liver problems: Cases of liver failure, including fatal cases, have been reported in patients receiving KYPROLIS. Your liver function should be closely monitored during treatment. Blood problems: Cases of a blood disease called thrombotic microangiopathy, including thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), including fatal cases, have been reported in patients who received KYPROLIS. Your doctor should monitor your signs and symptoms patients 389 patients TALK TO YOUR DOCTOR ABOUT YOUR LENGTH OF TREATMENT. Please see additional Important Safety Information on page

12 K+d: TWICE WEEKLY* Consider the proven results of KYPROLIS (carfilzomib) and dexamethasone vs Velcade (bortezomib) and dexamethasone. In a clinical study, patients receiving KYPROLIS and dexamethasone* lived twice as long without their disease getting worse months (median ) 9.4 months (median ) KYPROLIS +dexamethasone (K+d)* results (464 patients) VS Velcade +dexamethasone (V+d) results (465 patients) Emmett s doctor explained that in the clinical study almost 8 10 OUT OF patients responded to treatment with K+d. 4, * *K+d 56 mg/m 2 twice weekly. Based on a clinical study of 929 patients with relapsed or refractory multiple myeloma who had received 1-3 prior therapies, 464 patients received KYPROLIS in combination with dexamethasone, and 465 received Velcade in combination with dexamethasone. The study compared how long patients lived without their disease getting worse and how patients responded to treatment. 4 The median is the middle number in a group of numbers arranged from lowest to highest. Continue to see how many patients with relapsed multiple myeloma achieved complete response or better in clinical studies. Brain problems: A nerve disease called Posterior Reversible Encephalopathy Syndrome (PRES), formerly called Reversible Posterior Leukoencephalopathy Syndrome (RPLS), has been reported in patients receiving KYPROLIS. It can cause seizure, headache, lack of energy, confusion, blindness, altered consciousness, and other visual and nerve disturbances, along with high blood pressure. Your doctor should monitor your signs and symptoms. Please see additional Important Safety Information on page

13 PATIENTS (%) More patients on a K+d * regimen had a response to treatment. 4 CLINICAL STUDY RESULTS: PATIENTS ON K+d* vs V+d 77% 63% OVERALL RESPONSE RATE (Partial Response or better) 54% 29% VERY GOOD PARTIAL RESPONSE or better Key: 13% 6% COMPLETE RESPONSE or better K+d* 464 patients V+d 465 patients 2xAS MANY PATIENTS achieved a complete response or better with K+d* than V+d 4 The longer patients stayed on treatment, the better their chances of reaching Complete Response (CR) or better. 8 MORE PATIENTS ON K+d* vs V+d REACHED CR OR BETTER AT EVERY TIME POINT MEASURED WHAT DO THE RESPONSE RATES MEAN? 1,3 Overall Response Rate = The percentage of patients in the clinical study with at least a partial response to treatment Very Good Partial Response or better = The percentage of patients in the clinical study with at least a very good partial response Complete Response or better = The percentage of patients in the clinical study with at least a complete response CUMULATIVE PERCENTAGE OF PATIENTS REACHING CR OR BETTER (%) Emmett understands that staying on treatment as long as possible can help him achieve a better response PATIENTS ON K+d* 464 patients PATIENTS ON V+d 465 patients TALK TO YOUR DOCTOR ABOUT YOUR LENGTH OF TREATMENT. TIME FROM START OF TREATMENT Your doctor may stop your treatment if you experience side effects that cannot be managed *K+d 56 mg/m 2 twice weekly. After the initial results of the clinical study were reported, the investigators decided to look at the cumulative number of patients who reached a complete response or better over time. This was not an objective of the clinical study. KYPROLIS should not be combined with melphalan and prednisone: Newly diagnosed transplant ineligible multiple myeloma patients have shown an increased risk of serious and fatal side effects when using KYPROLIS in combination with melphalan and prednisone. Please see additional Important Safety Information on page

14 K+d: ONCE WEEKLY* Consider the proven results of KYPROLIS (carfilzomib) plus dexamethasone once weekly. In a clinical study, patients receiving KYPROLIS +dexamethasone once weekly* lived more than 3 months longer without their disease getting worse vs patients receiving KYPROLIS +dexamethasone twice weekly. 4, 11.2 months (median ) 7.6 months (median ) KYPROLIS +dexamethasone (K+d)* results (240 patients) VS KYPROLIS +dexamethasone (K+d) results (238 patients) Emmett s doctor explained that in a clinical study 50 % MORE patients responded to treatment with K+d once weekly* vs K+d twice weekly 4, *K+d 70 mg/m 2 once weekly. Based on a clinical study of 478 patients with relapsed or refractory multiple myeloma who had received 2 to 3 prior therapies, 240 patients received KYPROLIS +dexamethasone once weekly and 238 patients received KYPROLIS +dexamethasone twice weekly. The study compared how long patients lived without their disease getting worse, and how patients responded to treatment. 4 K+d 27 mg/m 2 twice weekly. 27 mg/m 2 is not an FDA approved dose for KYPROLIS. The median is the middle number in a group of numbers arranged from lowest to highest. Continue to see how many patients with relapsed multiple myeloma achieved complete response or better in clinical studies. Possible fetal harm: KYPROLIS can cause harm to a fetus (unborn baby) when given to a pregnant woman. Women should avoid becoming pregnant during treatment with KYPROLIS and for 6 months following the final dose. Men should avoid fathering a child during treatment with KYPROLIS and for 3 months following the final dose. KYPROLIS can cause harm to a fetus if used during pregnancy or if you or your partner become pregnant during treatment with KYPROLIS. Please see additional Important Safety Information on page

15 More patients on a once weekly regimen had a response to treatment. 4 CLINICAL STUDY RESULTS: PATIENTS ON K+d ONCE WEEKLY* vs K+d TWICE WEEKLY Key: K+d ONCE WEEKLY* 240 patients K+d TWICE WEEKLY 238 patients % PATIENTS (%) % OVERALL RESPONSE RATE (Partial Response or better) 34.2% 13.4% VERY GOOD PARTIAL RESPONSE or better 7.1% 1.7% COMPLETE RESPONSE or better 4xAS MANY PATIENTS achieved a complete MORE THAN response or better with K+d once weekly* vs K+d twice weekly WHAT DO THE RESPONSE RATES MEAN? 1,3 Overall Response Rate = The percentage of patients in the clinical study with at least a partial response to treatment Very Good Partial Response or better = The percentage of patients in the clinical study with at least a very good partial response Complete Response or better = The percentage of patients in the clinical study with at least a complete response *K+d 70 mg/m 2 once weekly. K+d 27 mg/m 2 twice weekly. 27 mg/m 2 is not an FDA approved dose for KYPROLIS. What are the possible side effects of KYPROLIS (carfilzomib)? The most common side effects occurring in at least 20% of patients receiving KYPROLIS in the combination therapy trials are: low red blood cell count, low white blood cell count, diarrhea, difficulty breathing, tiredness (fatigue), low platelets, fever, sleeplessness (insomnia), muscle spasm, cough, upper airway (respiratory tract) infection, and decreased potassium levels. Please see additional Important Safety Information on page

16 Understand the steps on your treatment journey. MAKE A PLAN, AND WORK IT! 1: SET YOUR GOALS 3: PREPARE FOR CHALLENGES 2: COMMIT TO THE DOSING REGIMEN 4: REACH & MANAGE YOUR BEST RESPONSE 16

17 IMPORTANT SAFETY INFORMATION KYPROLIS (carfilzomib) can cause serious side effects: Heart problems: KYPROLIS can cause heart problems or worsen pre-existing heart conditions. Death due to cardiac arrest has occurred within one day of KYPROLIS administration. Before starting KYPROLIS, you should have a full medical work-up (including blood pressure and fluid management). You should be closely monitored during treatment. Kidney problems: There have been reports of sudden kidney failure in patients receiving KYPROLIS. Your kidney function should be closely monitored during treatment. Tumor lysis syndrome (TLS): Cases of TLS have been reported in patients receiving KYPROLIS, including fatalities. You should be closely monitored during treatment for any signs of TLS. Lung damage: Cases of lung damage have been reported in patients receiving KYPROLIS, including fatal cases. Pulmonary hypertension (high blood pressure in the lungs): There have been reports of pulmonary hypertension in patients receiving KYPROLIS. Lung complications: Shortness of breath was reported in patients receiving KYPROLIS. Your lung function should be closely monitored during treatment. High blood pressure: Cases of high blood pressure, including fatal cases, have been reported in patients receiving KYPROLIS. Your blood pressure should be closely monitored during treatment. Blood clots: There have been reports of blood clots in patients receiving KYPROLIS. If you are at high risk for blood clots, your doctor can recommend ways to lower the risk. If you are using KYPROLIS in combination with dexamethasone or with lenalidomide plus dexamethasone, your doctor should assess and may prescribe another medicine to help lower your risk for blood clots. If you are using birth control pills or other medical forms of birth control associated with a risk of blood clots, talk to your doctor and consider a different method of birth control during treatment with KYPROLIS in combination with dexamethasone or with lenalidomide plus dexamethasone. Infusion reactions: Symptoms of infusion reactions included fever, chills, joint pain, muscle pain, facial flushing and/or swelling, vomiting, weakness, shortness of breath, low blood pressure, fainting, chest tightness, and chest pain. These symptoms can occur immediately following infusion or up to 24 hours after administration of KYPROLIS. If you experience any of these symptoms, contact your doctor immediately. Severe bleeding problems: Fatal or serious cases of bleeding problems have been reported in patients receiving KYPROLIS. Your doctor should monitor your signs and symptoms of blood loss. Very low platelet count: Low platelet levels can cause unusual bruising and bleeding. You should have regular blood tests to check your platelet count during treatment. Liver problems: Cases of liver failure, including fatal cases, have been reported in patients receiving KYPROLIS. Your liver function should be closely monitored during treatment. Blood problems: Cases of a blood disease called thrombotic microangiopathy, including thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), including fatal cases, have been reported in patients who received KYPROLIS. Your doctor should monitor your signs and symptoms. Brain problems: A nerve disease called Posterior Reversible Encephalopathy Syndrome (PRES), formerly called Reversible Posterior Leukoencephalopathy Syndrome (RPLS), has been reported in patients receiving KYPROLIS. It can cause seizure, headache, lack of energy, confusion, blindness, altered consciousness, and other visual and nerve disturbances, along with high blood pressure. Your doctor should monitor your signs and symptoms. KYPROLIS should not be combined with melphalan and prednisone: Newly diagnosed transplant ineligible multiple myeloma patients have shown an increased risk of serious and fatal side effects when using KYPROLIS in combination with melphalan and prednisone. Possible fetal harm: KYPROLIS can cause harm to a fetus (unborn baby) when given to a pregnant woman. Women should avoid becoming pregnant during treatment with KYPROLIS and for 6 months following the final dose. Men should avoid fathering a child during treatment with KYPROLIS and for 3 months following the final dose. KYPROLIS can cause harm to a fetus if used during pregnancy or if you or your partner become pregnant during treatment with KYPROLIS. You should contact your doctor immediately if you experience any of the following: Shortness of breath Prolonged, unusual or excessive bleeding Yellowing of the skin and/or eyes (jaundice) Headaches, confusion, seizures, or loss of sight Pregnancy (women should not receive KYPROLIS if they are pregnant or breastfeeding) Any other side effect that bothers you or does not go away What are the possible side effects of KYPROLIS? The most common side effects occurring in at least 20% of patients receiving KYPROLIS in the combination therapy trials are: low red blood cell count, low white blood cell count, diarrhea, difficulty breathing, tiredness (fatigue), low platelets, fever, sleeplessness (insomnia), muscle spasm, cough, upper airway (respiratory tract) infection, and decreased potassium levels. These are not all the possible side effects of KYPROLIS. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit medwatch or call FDA Please see Full Product Information. 17

18 Notes 18

19 Multiple myeloma relapses happen. Work with your doctor to reach and manage your relapse treatment goals. Visit kyprolis.com to learn more. Heart problems: KYPROLIS can cause heart problems or worsen pre-existing heart conditions. Death due to cardiac arrest has occurred within one day of KYPROLIS administration. Before starting KYPROLIS, you should have a full medical work-up (including blood pressure and fluid management). You should be closely monitored during treatment. Please see additional Important Safety Information on page 17. References: 1. Glossary. Multiple Myeloma Research Foundation website. Accessed October 29, National Cancer Institute website. Accessed October 29, Referenced with permission from the NCCN Clinical Practice Guidelines In Oncology (NCCN Guidelines ) for Multiple Myeloma V National Comprehensive Cancer Network, Inc All rights reserved. Accessed October 29, To view the most recent and complete version of the guideline, go online to NCCN.org. 4. KYPROLIS (carfilzomib) prescribing information, Onyx Pharmaceuticals Inc., an Amgen Inc. subsidiary. 5. National Cancer Institute website. Accessed October 29, American Cancer Society website. Accessed October 29, Dimopoulos M, Wang M, Maisnar V, et al. Response and progression-free survival according to planned treatment duration in patients with relapsed multiple myeloma treated with carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide and dexamethasone (Rd) in the phase III ASPIRE study. J Hematol Oncol. 2018;11: Data on file, Amgen; Support, Simplified. Revlimid (lenalidomide) is a product of Celgene Corporation. Velcade (bortezomib) is a product of Millennium Pharmaceuticals, Inc Amgen Inc. All rights reserved. Not for reproduction. USA November 2018